Single-Molecule Imaging Demonstrates Ligand Regulation of the Oligomeric Status of CXCR4 in Living Cells
Single-Molecule Imaging Demonstrates Ligand Regulation of the Oligomeric Status of CXCR4 in Living Cells
复制标题
单分子成像显示活细胞中 CXCR4 寡聚状态的配体调节
DOI：
10.1021/acs.jpcb.6b10969
复制
发表时间：
2017-02-23
影响因子：
3.3
通讯作者：
Huang, Fang
中科院分区：
文献类型：
--
作者：
Lao, Jun;He, Hua;Huang, Fang
g蛋白偶联受体的二聚化和寡聚化在其信号转导中的作用是非常有争议的。描述这一问题可以极大地促进药物的合理设计。通过单分子成像，我们发现趋化因子受体CXCR4主要以单体形式存在于正常哺乳动物活细胞中，并以高表达水平形成二聚体和高阶低聚体，例如在癌细胞中。趋化实验表明，CXCR4的信号转导活性不仅依赖于其表达水平，与CXCR4的寡聚状态密切相关。此外，结合配体可以有效上调或下调CXCR4的低聚体水平，这表明结合配体可能通过调节CXCR4的低聚体状态而不是简单地诱导构象变化来实现其关键作用。
The role of dimerization and oligomerization of G-protein-coupled receptors in their signal transduction is highly controversial. Delineating this issue can greatly facilitate rational drug design. With single-molecule imaging, we show that chemokine receptor CXCR4 exists mainly as a monomer in normal mammalian living cells and forms dimers and higher-order oligomers at a high expression level, such as in cancer cells. Chemotaxis tests demonstrate that the signal transduction activity of CXCR4 does not depend only on its expression level, indicating a close relation with the oligomeric status of CXCR4. Moreover, binding ligands can effectively upregulate or downregulate the oligomeric level of CXCR4, which suggests that binding ligands may realize their pivotal roles by regulating the oligomeric status of CXCR4 rather than by simply inducing conformational changes.